SWOG-9320 Combination Chemotherapy, Radiation Therapy, and Antiviral Therapy in Treating Patients With AIDS-Related Lymphoma

Sponsor

Southwest Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00002571

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

205

Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Antiviral therapy may be effective treatment for AIDS-related lymphoma.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, radiation therapy, and antiviral therapy in treating patients who have AIDS-related lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: bleomycin sulfate Biological: filgrastim Drug: cyclophosphamide Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: methotrexate Drug: prednisone Drug: trimethoprim-sulfamethoxazole Drug: vincristine sulfate Radiation: radiation therapy Drug: Intrathecal cytarabine	Phase 2

Detailed Description

OBJECTIVES: I. Assess the response rate of AIDS-related lymphoma to ProMACE-CytaBOM (cyclophosphamide, doxorubicin, etoposide, prednisone, cytarabine, bleomycin, vincristine, methotrexate). II. Assess the toxic effects of ProMACE-CytaBOM in patients with AIDS-related lymphoma. III. Evaluate whether the incorporation of filgrastim (G-CSF) into the regimen allows treatment with full doses of the myelotoxic agents in these patients. IV. Determine whether intensive CNS treatment with intrathecal cytarabine and whole-brain irradiation prevents meningeal relapse or controls meningeal lymphomatous involvement in these patients.

OUTLINE: Patients are stratified according to participating institution and descriptive factors: histopathology (diffuse large cleaved/noncleaved and immunoblastic lymphomas vs all others), CD4 count (less than 50 vs 50 or more cells/mm3), prior opportunistic infection (yes vs no), performance status (0 and 1 vs 2), concurrent AZT (yes vs no), concurrent protease inhibitors (yes vs no), marrow involvement (yes vs no). Patients receive ProMACE-CytaBOM regimen as follows: Cyclophosphamide, doxorubicin, and etoposide IV on day 1 Cytarabine, bleomycin, vincristine, and methotrexate IV on day 8 Oral prednisone on days 1-14 Oral leucovorin calcium every 6 hours for 4 doses on day 9 Patients also receive filgrastim (G-CSF) subcutaneously on days 9-20 and oral co-trimoxazole 3 days a week throughout treatment, plus antiretroviral therapy at the discretion of the treating physician. Treatment repeats every 21 days for a maximum of 6 courses. Patients with progressive disease are removed from study after 2 courses. Remaining patients receive an additional 2 treatment courses and are then restaged. Patients without stable or progressive disease receive 2 more courses in the absence of unacceptable toxicity. Patients with positive bone marrow at study entry receive CNS prophylaxis with 5 evenly spaced doses of intrathecal cytarabine during the first 2 treatment courses and on day 1 of each subsequent course. Patients with positive CSF cytology at study entry receive intrathecal cytarabine on days 1-5 of the first treatment course and on day 1 of each subsequent course if CSF negative after 5 daily doses. Patients whose CSF remains positive after 5 days receive 5 evenly spaced doses of intrathecal methotrexate during the second treatment course. Patients with negative bone marrow and CSF cytology at study entry receive 5 evenly spaced doses of intrathecal cytarabine within 1 month of systemic therapy. All patients achieving a complete or partial response following systemic therapy and intrathecal cytarabine receive cranial irradiation to all meningeal surfaces. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over approximately 2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II

Study Start Date :

Jun 1, 1994

Actual Primary Completion Date :

Nov 1, 2003

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ProMACE-CytaBOM + G-CSF 6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.	Biological: bleomycin sulfate 5u/m2 IV Q21days x 6 cycles Biological: filgrastim 5ug/kg SC, Days 9-20, Q 21 days x 6 cycles Other Names: G-CSF Drug: cyclophosphamide 490 mg/m2 IV Q 21 days x 6 cycles Drug: cytarabine 225 mg/m2 IV Q 21 days x 6 cycles Drug: doxorubicin hydrochloride 19 mg/m2 IV Q 21 days x 6 cycles Drug: etoposide 90 mg/m2 IV Q 21 days x 6 cycles Other Names: VP-16 Drug: leucovorin calcium 25 mg/m2 po 24 hours after methotrexate Q 6 hours x 4 doses for 6 cycles. Drug: methotrexate 90 mg/m2 IV, Q 21 days x 6 cycles. Drug: prednisone 60 mg/m2 po QD x 14days for 6 cycles Drug: trimethoprim-sulfamethoxazole 1 double throughout strength treatment tablet po on Monday, Wednesday, and Friday x 6, 21 day cycles Other Names: TMP/SMX Drug: vincristine sulfate 1.4 mg/m2 IV Q 21 Days x 6 cycles Radiation: radiation therapy All patients achieving a CR or PR following systemic therapy and IT Ara-C, will receive 2,400 cGy in two hundred cGy fractions to the whole brain. Fields should adequately encompass all meningeal surfaces. Drug: Intrathecal cytarabine If initial bone marrow positive: Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first two cycles of therapy. Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle. If initial CSF cytology positive: Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first cycle of therapy. If CSF negative after above, Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle. If CSF positive after initial five doses of Ara-C, IT MTX 12 mg per dose x 5 doses should be given spaced evenly during the second cycle of therapy. If initial bone marrow and CSF negative: Ara-C 30 mg/m2 IT per dose x 5 doses to be given spaced evenly within 1 month of completion of systemic therapy. Other Names: IT Ara-C

Arm

Intervention/Treatment

Experimental: ProMACE-CytaBOM + G-CSF

6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.

Biological: bleomycin sulfate

5u/m2 IV Q21days x 6 cycles

Biological: filgrastim

5ug/kg SC, Days 9-20, Q 21 days x 6 cycles

Other Names:

G-CSF

Drug: cyclophosphamide

490 mg/m2 IV Q 21 days x 6 cycles

Drug: cytarabine

225 mg/m2 IV Q 21 days x 6 cycles

Drug: doxorubicin hydrochloride

19 mg/m2 IV Q 21 days x 6 cycles

Drug: etoposide

90 mg/m2 IV Q 21 days x 6 cycles

Other Names:

VP-16

Drug: leucovorin calcium

25 mg/m2 po 24 hours after methotrexate Q 6 hours x 4 doses for 6 cycles.

Drug: methotrexate

90 mg/m2 IV, Q 21 days x 6 cycles.

Drug: prednisone

60 mg/m2 po QD x 14days for 6 cycles

Drug: trimethoprim-sulfamethoxazole

1 double throughout strength treatment tablet po on Monday, Wednesday, and Friday x 6, 21 day cycles

Other Names:

TMP/SMX

Drug: vincristine sulfate

1.4 mg/m2 IV Q 21 Days x 6 cycles

Radiation: radiation therapy

All patients achieving a CR or PR following systemic therapy and IT Ara-C, will receive 2,400 cGy in two hundred cGy fractions to the whole brain. Fields should adequately encompass all meningeal surfaces.

Drug: Intrathecal cytarabine

If initial bone marrow positive: Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first two cycles of therapy. Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle. If initial CSF cytology positive: Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first cycle of therapy. If CSF negative after above, Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle. If CSF positive after initial five doses of Ara-C, IT MTX 12 mg per dose x 5 doses should be given spaced evenly during the second cycle of therapy. If initial bone marrow and CSF negative: Ara-C 30 mg/m2 IT per dose x 5 doses to be given spaced evenly within 1 month of completion of systemic therapy.

Other Names:

IT Ara-C

Outcome Measures

Primary Outcome Measures

Response [every 3 months while on protocol treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically proven intermediate or high grade non-Hodgkin's lymphoma of one of the following histologies: Follicular, predominantly large cell Diffuse, small cleaved cell Diffuse mixed, small and large cell Diffuse, large cell (cleaved or noncleaved) Immunoblastic, large cell Small noncleaved cell, Burkitt's or non-Burkitt's No lymphoblastic lymphoma Prior diagnosis of AIDS or HIV positivity required Confirmation of HIV antibody status by Western blot mandatory Bidimensionally measurable or evaluable disease No primary CNS lymphoma Concurrent registration on protocol SWOG-8947 (central serum repository) required

PATIENT CHARACTERISTICS: Age: Over 18 Performance status: SWOG 0-2 Hematopoietic: Absolute neutrophil count at least 500/mm3 Platelet count at least 75,000/mm3 Hepatic: AST no greater than 1.5 times normal Alkaline phosphatase no greater than 1.5 times normal LDH no greater than 1.5 times normal PT/PTT normal Renal: Creatinine no greater than 2.0 times normal Creatinine clearance at least 60 mL/min Cardiovascular: No serious abnormalities on EKG No history of severe coronary artery disease No history of cardiomyopathy, congestive heart failure, or arrhythmia Other: No active uncontrolled infection No active second malignancy within 5 years except adequately treated nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for lymphoma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MBCCOP - University of South Alabama	Mobile	Alabama	United States	36688
2	CCOP - Greater Phoenix	Phoenix	Arizona	United States	85006-2726
3	Veterans Affairs Medical Center - Phoenix (Hayden)	Phoenix	Arizona	United States	85012
4	Veterans Affairs Medical Center - Tucson	Tucson	Arizona	United States	85723
5	Arizona Cancer Center	Tucson	Arizona	United States	85724
6	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas	United States	72205
8	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
9	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033-0800
10	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
11	Beckman Research Institute, City of Hope	Los Angeles	California	United States	91010
12	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California	United States	94553
13	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
14	Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
15	University of California Davis Medical Center	Sacramento	California	United States	95817
16	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
17	David Grant Medical Center	Travis Air Force Base	California	United States	94535
18	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
19	University of Colorado Cancer Center	Denver	Colorado	United States	80262
20	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
21	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
22	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859-5000
23	CCOP - Central Illinois	Decatur	Illinois	United States	62526
24	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois	United States	60141
25	Loyola University Medical Center	Maywood	Illinois	United States	60153
26	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
27	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
28	Veterans Affairs Medical Center - Wichita	Wichita	Kansas	United States	67218
29	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky	United States	40511-1093
30	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
31	MBCCOP - LSU Medical Center	New Orleans	Louisiana	United States	70112
32	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
33	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
34	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana	United States	71130-3932
35	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71130
36	Boston Medical Center	Boston	Massachusetts	United States	02118
37	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts	United States	02130
38	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan	United States	48105
39	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
40	Veterans Affairs Medical Center - Detroit	Detroit	Michigan	United States	48201-1932
41	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
42	Henry Ford Hospital	Detroit	Michigan	United States	48202
43	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
44	Providence Hospital - Southfield	Southfield	Michigan	United States	48075-9975
45	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi	United States	39531-2410
46	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
47	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi	United States	39216
48	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi	United States	39534-2576
49	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri	United States	64128
50	CCOP - Kansas City	Kansas City	Missouri	United States	64131
51	St. Louis University Health Sciences Center	Saint Louis	Missouri	United States	63110-0250
52	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
53	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
54	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
55	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico	United States	87108-5138
56	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico	United States	87131
57	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
58	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio	United States	45219
59	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio	United States	45220-2288
60	Cleveland Clinic Cancer Center	Cleveland	Ohio	United States	44195
61	CCOP - Columbus	Columbus	Ohio	United States	43206
62	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
63	CCOP - Dayton	Kettering	Ohio	United States	45429
64	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
65	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma	United States	73104
66	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon	United States	97201-3098
67	Veterans Affairs Medical Center - Portland	Portland	Oregon	United States	97207
68	CCOP - Columbia River Program	Portland	Oregon	United States	97213
69	CCOP - Greenville	Greenville	South Carolina	United States	29615
70	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
71	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
72	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
73	University of Texas Medical Branch	Galveston	Texas	United States	77555-1329
74	Texas Tech University Health Science Center	Lubbock	Texas	United States	79423
75	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
76	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78284
77	Veterans Affairs Medical Center - Temple	Temple	Texas	United States	76504
78	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
79	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132
80	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah	United States	84148
81	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
82	Swedish Cancer Institute	Seattle	Washington	United States	98104
83	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
84	Puget Sound Oncology Consortium	Seattle	Washington	United States	98109
85	CCOP - Northwest	Tacoma	Washington	United States	98405-0986